1. Field of the Invention
This invention resides in the field of sensors for detecting and measuring the concentration of gaseous analytes.
2. Description of the Prior Art
Trace gas analysis is of value in many applications, including the diagnosis and management of physiological conditions. A change in nitric oxide (NO) concentration in the exhaled breath of a person suffering from asthma, for example, can indicate a change in the level of inflammation in the airway of the person, which in turn can indicate an increase in the likelihood of an asthma attack. Another example of a trace gas in exhaled breath that is indicative of an abnormal physiological condition is carbon monoxide. A rise in the carbon monoxide level in exhaled breath can be an early sign of the onset of hemolytic jaundice. A still further example is hydrogen, a rise in which can indicate malabsorption of carbohydrate. In certain cases, these gases are present at concentrations in the parts per billion (ppb) range, and changes within this range can indicate abnormalities before they can be detected at the parts per million range.
Various sensors have been developed to measure the concentrations of different gaseous analytes. Some of these sensors contain bioactive substances, notably proteins, which undergo measurable changes upon contact with gaseous analytes and can therefore be termed “chemical transducers” since they transform the change into a signal that can be read and quantified. One such bioactive substance is cytochrome c, which undergoes an optically quantifiable change in response to NO. Certain sensors that utilize cytochrome c include this protein in encapsulated form in a xerogel (a dry stabilized sol-gel). Sensors of the type and related technology are disclosed in the following U.S. published patent applications and patents: US 2004-0017570 A1, published Jan. 29, 2004 (application Ser. No. 10/334,625, filed Dec. 30, 2002); US 2005-0053549 A1, published Mar. 10, 2005 (application Ser. No. 10/659,408, filed Sep. 10, 2003); US 2005-0083527 A1, published Apr. 21, 2005 (application Ser. No. 10/767,709, filed Jan. 28, 2004); U.S. Pat. No. 5,795,187, issued Aug. 18, 1998; and U.S. Pat. No. 6,010,459, issued Jan. 4, 2000. The disclosures of each of the patents and patent applications listed in this paragraph are hereby incorporated herein by reference.
Unfortunately, certain proteins that are used as trace gas sensors by virtue of detectable changes in the proteins are susceptible to degradation over time. The term “degradation” is used herein to denote a loss in the functionality of the protein, including the responsivity of the protein to the analyte in terms of both the magnitude of the change that can be detected and the time required for the change to occur. In extreme cases, the sensor may have degraded to the point of being useless, i.e., incapable of producing a meaningful or reliable analysis, by the time the user is ready to perform the analysis or even by the time the user obtains a unit containing the sensor. In cytochrome c, for example, a loss of responsivity to NO is evidenced by a loss in the magnitude of the soret peak, which is the spectral peak of the iron porphyrin, the part of the protein that binds NO, and is centered around 400 nm. This degradation has been found to limit the utility of cytochrome c as a sensor in certain circumstances. While the rate of degradation appears to vary with temperature, the mechanism and overall cause of the degradation are unknown. Sensors that display a rapid response are particularly susceptible to degradation. This is true for example in certain cytochrome c elements that are disclosed in the citations above, particularly such elements that are able to generate a signal in less than five minutes of exposure to NO.